Comparative Immunohistochemistry of Placental Corticotropin-Releasing Hormone and the Transcription Factor RelB-NFκB2 Between Humans and Nonhuman Primates

Abstract

The transcription factor RelB-NFκB2, activated by the noncanonical NFκB pathway, positively regulates corticotropin-releasing hormone (CRH) and prostaglandin production in the term human placenta and may play an important role in the timing of human parturition. Here we explored whether RelB-NFκB2 signaling plays a role in parturition in nonhuman anthropoid primates. We performed immunohistochemical staining to assess the correlation between CRH and nuclear activity of RelB-NFκB2 heterodimers in term placentas from humans, 3 catarrhine primate species, and a single platyrrhine primate species. Consistent with our previous studies, the human placenta showed cytoplasmic staining for CRH and nuclear staining for RelB-NFκB2. Similar staining patterns were noted in the 3 catarrhine primates (chimpanzee, baboon, and rhesus macaque). The platyrrhine (marmoset) placentas stained positively for CRH and RelB but not for NFκB2. Catarrhine (but not platyrrhine) nonhuman primate term placentas demonstrate the same CRH staining and nuclear localization patterns of RelB and NFκB2 as does human placenta. These results suggest that catarrhine primates, particularly rhesus macaques, may serve as useful animal models to study the biologic significance of the noncanonical NFκB pathway in human pregnancy.

Figure 1.

Representative immunohistochemical staining of CRH, RelB, and NFκB2 in 3 independent placentas from each species studied. When inactive, p65, a subunit in the canonical NFκB signaling pathway, is sequestered in the cytoplasm; its identification in the cytoplasm served as a positive control. CD45, a receptor-linked protein tyrosine phosphatase that is expressed in leukocytes but not the placental trophoblast, was used as the negative control. Original magnification, ×200.